The Interplay between HGF/c-met Axis and Nox4 in BRAF Mutated Melanoma

Background: Melanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases, have a role in the development and progression of melanocytic lesions and malignant melanoma. Among those, the hepatocyte growth factor (HGF)/c-met axis is emerging as a critical player because it can play a role in drug resistance. Indeed, 50% of melanoma patients present BRAF mutations, however, all responders develop resistance to the inhibitors typically within one year of treatment. Interestingly, BRAF inhibitors induce reactive oxygen species (ROS) in melanoma cells, therefore, the aim of this study was to investigate a possible interplay between HGF/c-met and ROS sources, such as NADPH oxidases (Nox). Methods: The expression of c-met and Nox were quantified in 60 patients with primary cutaneous melanoma. In vitro experiments on melanoma primary cells and the cell line were performed to dissect the underpinned molecular mechanism. Results: The outcome of interest was the correlation between the high positivity for both Nox4 and c-met and metastasis occurring at least 1 year later than melanoma diagnosis in BRAF mutated patients, in contrast to nonmutated. In vitro experiments demonstrated that the axis HGF/c-met/Nox4/ROS triggers the epithelial-mesenchymal transition. Conclusions: The observed correlation suggests an interplay between c-met and Nox4 in promoting the onset of metastasis. This study suggests that Nox4 inhibitors could be associated to the current therapy used to treat melanoma patients with BRAF mutations.     

Pectin: A Long-Neglected Broad-Spectrum Antibacterial

First reported in the late 1930s and partly explained in 1970, the antibacterial activity of pectin remained almost ignored until the late 1990s. The concomitant emergence of research on natural antibacterials and new usages of pectin polysaccharides, including those in medicine widely researched in Russia, has led to a renaissance of research into the physiological properties of this uniquely versatile polysaccharide ubiquitous in plants and fruits. By collecting scattered information, this study provides an updated overview of the subtle factors affecting the behaviour of pectin as an antimicrobial. Less-degraded pectin extracted by acid-free routes, we argue in the conclusions, will soon find applications from new treatments for polymicrobial infections to use as an implantable biomaterial in tissue and bone engineering.     

The photoreceptive cells of the pineal gland in adult zebrafish (Danio rerio)

The zebrafish pineal gland plays a fundamental role in the regulation of the circadian rhythm through the melatonin secretion. The pinealocytes, also called photoreceptive cells, are considered the morphofunctional unit of pineal gland. In literature, the anatomical features, the cellular characteristics, and the pinealocytes morphology of zebrafish pineal gland have not been previously described in detail. Therefore, this study was undertaken to analyze the structure and ultrastructure, as well as the immunohistochemical profile of the zebrafish pineal gland with particular reference to the pinealocytes. Here, we demonstrated, using RT-PCR, immunohistochemistry and transmission electron microscopy, the expression of the mRNA for rhodopsin in the pineal gland of zebrafish, as well as its cellular localization exclusively in the pinealocytes of adult zebrafish. Moreover, the ultrastructural observations demonstrated that the pinealocytes were constituted by an outer segment with numerous lamellar membranes, an inner segment with many mitochondria, and a basal pole with the synapses. Our results taken together demonstrated a central role of zebrafish pinealocytes in the control of pineal gland functions.     

Moldless Printing of Silicone Lenses with Embedded Nanostructured Optical Filters

In this work, both light‐shaping and image magnification features are integrated into a single lens element using a moldless procedure that takes advantage of the physical and optical properties of mesoporous silicon (PSi) photonic crystal nanostructures. Casting of a liquid poly(dimethylsiloxane) pre‐polymer solution onto a PSi film generates a droplet with a contact angle that is readily controlled by the silicon nanostructure, and adhesion of the cured polymer to the PSi photonic crystal allows preparation of lightweight (10 mg) freestanding lenses (4.7 mm focal length) with an embedded optical component (e.g., optical rugate filter, resonant cavity, and distributed Bragg reflector). The fabrication process shows excellent reliability (yield 95%) and low cost and the lens is expected to have implications in a wide range of applications. As a proof‐of‐concept, using a single monolithic lens/filter element it is demonstrated: fluorescence imaging of isolated human cancer cells with rejection of the blue excitation light, through a lens that is self‐adhered to a commercial smartphone; shaping of the emission spectrum of a white light emitting diode to tune the color from red through blue; and selection of a narrow wavelength band (bandwidth 5 nm) from a fluorescent molecular probe.     

4D Printing of a Bioinspired Microneedle Array with Backward‐Facing Barbs for Enhanced Tissue Adhesion

Microneedle (MN), a miniaturized needle with a length‐scale of hundreds of micrometers, has received a great deal of attention because of its minimally invasive, pain‐free, and easy‐to‐use nature. However, a major challenge for controlled long‐term drug delivery or biosensing using MN is its low tissue adhesion. Although microscopic structures with high tissue adhesion are found from living creatures in nature (e.g., microhooks of parasites, barbed stingers of honeybees, quills of porcupines), creating MNs with such complex microscopic features is still challenging with traditional fabrication methods. Here, a MN with bioinspired backward‐facing curved barbs for enhanced tissue adhesion, manufactured by a digital light processing 3D printing technique, is presented. Backward‐facing barbs on a MN are created by desolvation‐induced deformation utilizing cross‐linking density gradient in a photocurable polymer. Barb thickness and bending curvature are controlled by printing parameters and material composition. It is demonstrated that tissue adhesion of a backward‐facing barbed MN is 18 times stronger than that of barbless MN. Also demonstrated is sustained drug release with barbed MNs in tissue. Improved tissue adhesion of the bioinspired MN allows for more stable and robust performance for drug delivery, biofluid collection, and biosensing.     

A labelling framework for probabilistic argumentation

The combination of argumentation and probability paves the way to new accounts of qualitative and quantitative uncertainty, thereby offering new theoretical and applicative opportunities. Due to a variety of interests, probabilistic argumentation is approached in the literature with different frameworks, pertaining to structured and abstract argumentation, and with respect to diverse types of uncertainty, in particular the uncertainty on the credibility of the premises, the uncertainty about which arguments to consider, and the uncertainty on the acceptance status of arguments or statements. Towards a general framework for probabilistic argumentation, we investigate a labelling-oriented framework encompassing a basic setting for rule-based argumentation and its (semi-) abstract account, along with diverse types of uncertainty. Our framework provides a systematic treatment of various kinds of uncertainty and of their relationships and allows us to back or question assertions from the literature.